Pharmacokinetics of vincristine sulfate in adult cancer patients.

Vincristine concentration in serum from 1 min to 72 hr was measured by radioimmunoassay in 14 patients with cancers following i.v. bolus injection of vincristine sulfate at 0.45 to 1.30 mg/sq m. The pharmacokinetic data were analyzed by a nonlinear least-square regression program NONLIN. A three-compartmental open model fitted the raw data better than a two-compartmental model. The mean half-lives of the triphasic decay curves alpha, beta, and gamma were 1.9, 19.2, and 1359 min (22.6 hr), respectively. The apparent volume of the central compartment and the volume of distribution at steady state (Vdss) per 1.73 sq m body surface area were 4.1 and 167.6 liters, respectively. The plasma clearance was 141.9 ml/min/1.73 sq m, and the area under the concentration X time curve from 0 to infinity (AUC0 infinity) for 2 mg vincristine was 21,689 nM.min. Linear regression analysis of the data gave evidence for increasing plasma clearance at higher doses of vincristine. In patients with higher platelet counts, lower AUC0 infinity values were obtained, suggesting a possible interaction of vincristine with blood platelets. Our results, a large Vdss, a long biological half-life, and a low rate-limiting rate constant from Compartment 3 to the central compartment (k31), indicate an avid tissue binding and a slow drug release from the body tissues which may account for drug-related neurotoxicity.